Production method of citalopram, intermediate therefor and production method of the intermediate

Abstract

Citalopram can be industrially and economically produced and at a high yield by reacting a compound of the following formula [VI] with 3-(dimethylamino)propyl chloride in the presence of at least one of N,N,N′,N′-tetramethylethylenediamine and 1,3-dimethyl-2-imidazolidinone and a condensing agent. The compound of the following formula [III], which is a key compound for the production of citalopram, can be easily produced by subjecting the compound of the following formula [II] to reduction and cyclization.

1 . A compound of the formula [I] 
       
         
           
           
               
               
           
         
       
     
     
         2 . A production method of a compound of the formula [I] 
       
         
           
           
               
               
           
         
       
       which comprises converting 4-bromofluorobenzene to 4-fluorophenylmagnesium bromide, and reacting the 4-fluorophenylmagnesium bromide with 2,4-dimethylbenzaldehyde.  
     
     
         3 . A production method of a compound of the formula [II] 
       
         
           
           
               
               
           
         
       
       which comprises oxidizing a compound of the formula [I] 
       
         
           
           
               
               
           
         
       
     
     
         4 . A production method of 1,3-dimethyl-4-(4′-fluorobenzoyl)benzene, which comprises subjecting m-xylene as a starting material and solvent to Friedel-Crafts reaction with 4-fluorobenzoyl halide.  
     
     
         5 . A production method of a compound of the formula [II] 
       
         
           
           
               
               
           
         
       
       which comprises subjecting m-xylene as a starting material and solvent to Friedel-Crafts reaction with 4-fluorobenzoyl halide to give 1,3-dimethyl-4-(4′-fluorobenzoyl)benzene and oxidizing said 1,3-dimethyl-4-(4′-fluorobenzoyl)benzene.  
     
     
         6 . A production method of a compound of the formula [II] 
       
         
           
           
               
               
           
         
       
       which comprises subjecting 2,4-dimethylbenzoyl halide to Friedel-Crafts reaction with fluorobenzene to give 1,3-dimethyl-4-(4′-fluorobenzoyl)benzene and oxidizing said 1,3-dimethyl-4-(4′-fluorobenzoyl)benzene.  
     
     
         7 . A production method of a compound of the formula [II] 
       
         
           
           
               
               
           
         
       
       which comprises subjecting trimellitic anhydride to Friedel-Crafts reaction with fluorobenzene in a dichloro-substituted or trichloro-substituted benzene solvent.  
     
     
         8 .- 20 . (Canceled)